Can long-term use of Diane 35 (cyproterone acetate and ethinyl estradiol) affect thyroid function, specifically lowering Thyroid-Stimulating Hormone (TSH) levels?

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Diane 35 and TSH Levels

Direct Answer

There is no evidence that long-term use of Diane 35 (cyproterone acetate and ethinyl estradiol) lowers TSH levels. The available research on Diane 35 focuses on its effects on sex hormones, ovarian function, and androgenic symptoms, with no documented impact on thyroid-stimulating hormone.

Evidence Review

Hormonal Effects of Diane 35

The documented hormonal changes from Diane 35 use include:

  • Suppression of gonadotropins (LH and FSH) with significant decreases in the LH/FSH ratio occurring after 3 cycles of treatment 1
  • Reduction in androgens including total testosterone (39% decrease), free testosterone (62% decrease), androstenedione, and DHEA-S levels 2, 1
  • Marked increase in sex hormone-binding globulin (SHBG) by approximately 3-fold during treatment cycles, which persists throughout therapy 2, 1
  • Modest increases in prolactin levels with an increasing tendency during treatment 3

Absence of Thyroid Effects

  • No thyroid hormone alterations documented: Multiple pharmacokinetic and hormonal studies of Diane 35 measured comprehensive hormone panels including LH, FSH, prolactin, estrogens, progesterone, and various androgens, but none reported changes in TSH, T3, or T4 levels 3, 2, 1
  • No clinical thyroid symptoms reported: Studies tracking side effects over treatment periods of 9-30 cycles documented weight gain, breast tenderness, mood changes, and blood pressure increases, but no thyroid-related symptoms 1

Important Distinction: Estrogen Effects on Thyroid Function

While Diane 35 does not lower TSH, it's important to understand that:

  • Estrogen-containing medications increase SHBG and thyroxine-binding globulin (TBG), which can affect total thyroid hormone levels but typically does not change TSH in euthyroid individuals 4
  • Patients with pre-existing hypothyroidism on levothyroxine may require dose adjustments when starting estrogen-containing contraceptives due to increased binding proteins, but this represents increased thyroid hormone requirements, not TSH suppression 4

Clinical Implications

  • TSH monitoring is not required specifically for Diane 35 use in women without pre-existing thyroid disease 3, 1
  • If TSH abnormalities occur in a patient taking Diane 35, investigate other causes of thyroid dysfunction rather than attributing it to the medication 5
  • For patients with hypothyroidism on levothyroxine, monitor TSH 6-8 weeks after starting Diane 35, as increased binding proteins may necessitate levothyroxine dose increases, but this is distinct from Diane 35 lowering TSH 6, 4

References

Research

Effects of a low-dose estrogen-antiandrogen combination (Diane-35) on clinical signs of androgenization, hormone profile and ovarian size in patients with polycystic ovary syndrome.

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 1989

Research

[Ovarian suppression with Diane 35/50].

Geburtshilfe und Frauenheilkunde, 1994

Research

Thyroid hormone replacement therapy.

Hormone research, 2001

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Initial Treatment for Elevated TSH

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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